DESCRIPTION (Applicant's abstract): We propose a novel high-throughput approach to the discovery of novel mitogens. We will use Random Activated Gene Expression (RAGE), which allows unbiased expression of full-length, or near full-length, transcripts of greater than 95 percent of the human genome in a library of only 5 million clones, to carry out a high throughput search for previously undiscovered mitogens. Our Phase I target populations will be conditionally immortal astrocytes and skeletal muscle cells, so as to reveal proteins of potential use in treatment of neuromuscular disease or CNS damage. The RAGE technology allows identification of the bioactive protein and large-scale production (e.g., 250 mg/liter) to be achieved within 10-14 weeks from the time of first identification of activity. Thus, this program also enables production of novel factors in sufficient quantity to support extensive biological analysis and commercial development. In addition to potential medical benefits, the discovery of new mitogens has considerable benefits on biological research in general. Even the limited number of growth factors available has provided a central foundation for, e.g., the nascent field of stem cell biology. Success in this Phase I program will enable a full-scale effort to rapidly identify novel mitogens for a wide range of cell types. PROPOSED COMMERCIAL APPLICATION: This project will enable the ready adaptation of the RAGE technology to virtually any functional genomics assay system, permitting the identification and characterization of a large number of novel proteins and genes that encode them. Thus not only will Athersys have a technology product but it will also have various therapeutic products that were identified by virtue of RAGE's use in an assay system.